ABSTRACT The goal of this SC3 grant is to develop modular chemical building blocks for use in lanthanide-based, multi-modal luminescent probes for bioimaging applications. The approach will utilize the properties of persistently luminescent nanoparticles (PNLPs), which can store excitation energy and thermally release it over time. The central hypothesis is that a PLNP can stimulate emission from a tethered lanthanide complex in situ, avoiding the need for excitation of the luminescent probe through tissue. A persistently luminescent probe that can emit low energy light in the tissue transparency window can potentially provide information on disease localization with only the use of a near-infrared (NIR) sensitive camera. Fluorescence imaging can provide sub mm resolution in vivo but the bottleneck for implementation is the poor tissue penetration of the photons needed for excitation, and of the probe emission itself (<1 cm). The approach within this grant has the potential to move fluorescence imaging past the in vivo bottleneck by increasing tissue penetration. It will improve on the resolution offered by other imaging techniques, offer higher sensitivity and will be able to be used without exposing patients to a radiation dose. The modular nature of the proposed PLNP constructs will allow for their customization on an application-needed basis; the tethered lanthanide complexes can report on their surroundings, providing information on pH and O2 concentrations and influence the construct's localization in the body.